Schistosomiasis is one of the world's greatest health problems, afflicting over 200 million people. We have been studying the biochemical and molecular mechanisms by which invasive larvae of Schistosoma mansoni initiate infection of the human host. We have determined which macromolecules are degraded as larvae invade skin and have purified the principal proteolytic enzyme that facilitates this invasion. We now will complete studies defining the structure of the active site of this proteinase using different peptide substrates. We will label the active site serine and purify its peptide for sequencing. We will also continue sequencing the protein from its amino-terminus. Having isolated several cDNA clones for the proteinase, we will sequence insert DNA from these clones and compare to amino acid sequences obtained from the purified protein. We can also use cDNA clones to study, by in situ hybridization, temporal expression of proteinase mRNA during development of cercariae in the snail host. Finally, having shown there is a host immune response to the proteinase, we will determine the onset, peak, and diminution of this response over the course of infection in two animal models.